Clomiphene is a selective estrogen receptor modulator related to tamoxifen. Clomiphene is a mixture of two geometric isomers, cis-clomiphene (or zuclomiphene) and trans-clomiphene, (or enclomiphene). Clomiphene is currently approved as a mixture of both cis- and trans-isomers, the cis-isomer being present as about 30% to 50% (Merck Manual) for the induction of ovulation in anovulatory women.
Methods for synthesizing clomiphene are known in the art. For example, U.S. Pat. No. 2,914,563, the contents of which are hereby incorporated by reference, describes the preparation of clomiphene (see Example 3 in particular). U.S. Pat. No. 3,848,030, the contents of which are hereby incorporated by reference, describes a method to separate the cis- and trans-isomers of clomiphene (see Examples 31 and 32 in particular).
Current methods for preparing clomiphene require the isolation of intermediates and exchange of solvents making the process difficult to streamline. Large scale production of clomiphene and purification of the trans-isomer of clomiphene would be greatly improved if clomiphene synthesis could be accomplished using a single solvent and without the need to isolate intermediates.